tbuckley/cabot-search huggingface dataset:
Effects of Tirzepatide Versus Insulin Glargine on Cystatin C–Based Kidney Function: A SURPASS-4 Post Hoc Analysis
Authors: Hiddo J.L. Heerspink, Naveed Sattar, Imre Pavo, Axel Haupt, Kevin L. Duffin, Zhengyu Yang, Russell J. Wiese, Jonathan M. Wilson, Andrea Hemmingway, David Z.I. Cherney, Katherine R. Tuttle
Journal: Diabetes Care (2023)

Tirzepatide reduces HbA1c and body weight, and creatinine-based estimated glomerular filtration rate (eGFR) decline. Unlike creatine-derived eGFR (eGFR-creatinine), cystatin C-derived eGFR (eGFR-cystatin C) is unaffected by muscle mass changes. We assessed effects of tirzepatide on eGFR-creatinine and eGFR-cystatin C.Our primary outcome was eGFR change from baseline at 52 weeks with pooled tirzepatide (5, 10, and 15 mg) and titrated insulin glargine in adults with type 2 diabetes and high cardiovascular risk (SURPASS-4).Least squares mean (SE) eGFR-creatinine (mL/min/1.73 m2) changes from baseline with tirzepatide and insulin glargine were -2.5 (0.38) and -3.9 (0.38) (between-group difference, 1.4 [95% CI 0.3-2.4]) and -3.5 (0.37) and -5.3 (0.37) (between-group difference, 1.8 [95% CI 0.8-2.8]) for eGFR-cystatin C. Baseline, 1-year, and 1-year change from baseline values significantly correlated between eGFR-cystatin C and eGFR-creatinine. Measures of eGFR changes did not correlate with body weight changes.Tirzepatide slows the eGFR decline rate, supporting a kidney-protective effect.
Surgeon Quality and Patient Survival After Resection for Non–Small-Cell Lung Cancer
Authors: Meredith A. Ray, Olawale Akinbobola, Carrie Fehnel, Andrea Saulsberry, Kourtney Dortch, Bradley Wolf, Ganpat Valaulikar, Hetal D. Patel, Thomas Ng, Todd Robbins, Matthew P. Smeltzer, Nicholas R. Faris, Raymond U. Osarogiagbon, Horace L. Wiggins, David Talton, Daniel R. Stevenson, Albert Koury
Journal: Journal of Clinical Oncology (2023)

The quality and outcomes of curative-intent lung cancer surgery vary in populations. Surgeons are key drivers of surgical quality. We examined the association between surgeon-level intermediate outcomes differences, patient survival differences, and potential mitigation by processes of care.
Nrf2 sensitizes ferroptosis through L-2-hydroxyglutarate-mediated chromatin modifications in sickle cell disease
Authors: Caixia Xi, Junfeng Pang, Wenbo Zhi, Chang-Sheng Chang, Umapathy Siddaramappa, Huidong Shi, Anatoli Horuzsko, Betty Pace, Xingguo Zhu
Journal: Blood (2023)
Reply to Z. Mai et al
Authors: Derya Tilki, Ming-Hui Chen, Anthony V. D'Amico
Journal: Journal of Clinical Oncology (2023)

We thank Mai et al 1 for giving us the opportunity to provide clarification on our recently published article. 2 We agree that the preradical prostatectomy prostate-specific antigen (PSA) level (>20, 10-20, <4 v 4-10 ng/mL [reference]), prostatectomy Gleason score (8-10, 7 v 6 [reference]), tumor category (T3b/4, T3a v T2 [reference]), and margin status (positive v negative [reference]) are all important predictors of both prostate cancer-specific and all-cause mortalities (PCSM, ACM).We mention in the statistical methods section that the model was adjusted for known prostate cancer prognostic factors, which included these factors.These adjustments were made to account for any differences that may exist between treatment groups as noted in Table 1 (Distribution of patient characteristics stratified by treatment).We did perform the same analyses evaluating for the end point of PCSM as mentioned in the results section.We found a very similar adjusted hazard ratio for PCSM as we did for ACM when comparing treatment initiating salvage radiation therapy at a PSA level of >0.25 ng/mL with 0.25 ng/mL or less.Specifically, these respective adjusted hazard ratios and 95% CIs were 1.43 (95% CI, 0.80 to 2.55) and 1.49 (95% CI, 1.11 to 2.00), but given a smaller number of prostate cancer as compared with all-cause deaths being 109 versus 1,269, respectively, the 95% CI for the adjusted hazard ratio for PCSM included 1.0.However, ACM is the most robust end point given that it is not subject to the potential for misclassification or ascertainment bias, which can exist when specifying a specific cause of death.
A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA
Authors: Emeline Colomba, Sarah Flora Jonas, Jean-Christophe Eymard, Rémi Delva, Pierre Emmanuel Brachet, Yann Neuzillet, Nicolas Penel, Guilhem Roubaud, Emmanuelle Bompas, Hakim Mahammedi, Raffaelle Longo, Carole Helissey, Philippe Barthélemy, Delphine Borchiellini, Ali Hasbini, Franck Priou, Carolina Saldana, Eric Voog, Bérangère Narcisso, Sylvain Ladoire, Jean-François Berdah, Jean-Baptiste Aisenfarb, Stéphanie Foulon, Karim Fizazi
Journal: European Urology (2023)
Society News
Journal: Neuro-Oncology (2023)

Journal Article Society News Get access Neuro-Oncology, Volume 25, Issue 6, June 2023, Page 1198, https://doi.org/10.1093/neuonc/noad077 Published: 02 June 2023 Article history Corrected and typeset: 02 June 2023 Published: 02 June 2023
Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study
Authors: James J Harding, Jia Fan, Do-Youn Oh, Hye Jin Choi, Jin Won Kim, Heung-Moon Chang, Lequn Bao, Hui-Chuan Sun, Teresa Macarulla, Feng Xie, Jean-Phillippe Metges, Jie'er Ying, John Bridgewater, Myung-Ah Lee, Mohamedtaki A Tejani, Emerson Y Chen, Dong Uk Kim, Harpreet Wasan, Michel Ducreux, Yuanyuan Bao, Lisa Boyken, Jiafang Ma, Phillip Garfin, Shubham Pant, Ghassan Abou-Alfa, Jorge Adeva Alfonso, Massimo Aglietta, Ari Baron, Muhammad Beg, Paula Carrasco Aguirre, Eric Chen, Ying Cheng, Antonio Cubillo Gracián, Laetitia Dahan, Filippo De Braud, Elisabetta Fenocchio, Olumide Gbolohon, Roopinder Gillmore, Marine Jary, Milind Javle, Yixing Jiang, Jung Hun Kang, Gentry George King, Madappa Kundranda, Laura Layos, Daneng Li, Tingbo Liang, Sara Lonardi, Omkar Marathe, Sebastian Mondaca, Andrés J. Muñoz Martin, Joon Oh Park, Roberto Pazo Cid, Paula Ribera Fernandez, Lorenza Rimassa, Rosa Rodriguez Alonso, Saeed Sadeghi, Aaron Scott, Benjamin Tan, David Tougeron, Qiang Yan, Xiaoyu Yin, Haitao Zhao
Journal: The Lancet Oncology (2023)
Rheumatology congresses post COVID-19: we cannot regress
Authors: Lena Bugge Nordberg, Jens Vikse, Marte Schrumpf Heiberg, Even Lillejordet, Marthe Thoresen Mæhlen, Eirik Klami Kristianslund, Sella Aarrestad Provan, Siri Lillegraven
Journal: The Lancet Rheumatology (2023)
When I use a word . . . Seeding trials
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

The recently published Lord O’Shaughnessy report on the conduct of commercially sponsored clinical trials of new medications in the UK contains 27 recommendations. Recommendation 22 reads “Financial incentives should be introduced for GPs to take part in commercial trials.” However, such payments, a feature of so-called seeding trials, have been considered unethical. Ethics committees should not approve any clinical trial in which investigators are given personal financial or other types of special incentives to take part in any way, including recruitment of patients.
Group A <i>Streptococcus</i> induces CD1a-autoreactive T cells and promotes psoriatic inflammation
Authors: Yi-Ling Chen, Jessica Soo Weei Ng, Rosana Ottakandathil Babu, Jeongmin Woo, Janina Nahler, Clare S. Hardman, Prathiba Kurupati, Lea Nussbaum, Fei Gao, Tao Dong, Kristin Ladell, David A. Price, David A. Duncan, David Johnson, Uzi Gileadi, Hashem Koohy, Graham S. Ogg
Journal: Science Immunology (2023)

Group A
Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems
Authors: Rochelle L. Castillo, Ikjot Sidhu, Igor Dolgalev, Tinyi Chu, Aleksandr Prystupa, Ipsita Subudhi, Di Yan, Piotr Konieczny, Brandon Hsieh, Rebecca H. Haberman, Shanmugapriya Selvaraj, Tomoe Shiomi, Rhina Medina, Parvathy Vasudevanpillai Girija, Adriana Heguy, Cynthia A. Loomis, Luis Chiriboga, Christopher Ritchlin, Maria De La Luz Garcia-Hernandez, John Carucci, Shane A. Meehan, Andrea L. Neimann, Johann E. Gudjonsson, Jose U. Scher, Shruti Naik
Journal: Science Immunology (2023)

Whereas the cellular and molecular features of human inflammatory skin diseases are well characterized, their tissue context and systemic impact remain poorly understood. We thus profiled human psoriasis (PsO) as a prototypic immune-mediated condition with a high predilection for extracutaneous involvement. Spatial transcriptomics (ST) analyses of 25 healthy, active lesion, and clinically uninvolved skin biopsies and integration with public single-cell transcriptomics data revealed marked differences in immune microniches between healthy and inflamed skin. Tissue-scale cartography further identified core disease features across all active lesions, including the emergence of an inflamed suprabasal epidermal state and the presence of B lymphocytes in lesional skin. Both lesional and distal nonlesional samples were stratified by skin disease severity and not by the presence of systemic disease. This segregation was driven by macrophage-, fibroblast-, and lymphatic-enriched spatial regions with gene signatures associated with metabolic dysfunction. Together, these findings suggest that mild and severe forms of PsO have distinct molecular features and that severe PsO may profoundly alter the cellular and metabolic composition of distal unaffected skin sites. In addition, our study provides a valuable resource for the research community to study spatial gene organization of healthy and inflamed human skin.
Chronic antigen in solid tumors drives a distinct program of T cell residence
Authors: Noah V. Gavil, Milcah C. Scott, Eyob Weyu, Olivia C. Smith, Stephen D. O’Flanagan, Sathi Wijeyesinghe, Sahar Lotfi-Emran, Stephen L. Shiao, Vaiva Vezys, David Masopust
Journal: Science Immunology (2023)

Analyses of healthy tissue reveal signatures that identify resident memory CD8
Genetic test “screening campaign” may be causing unnecessary alarm, experts warn
Authors: Elisabeth Mahase, Gareth Iacobucci
Journal: BMJ (2023)

A campaign to screen thousands of people for haemochromatosis using direct-to-consumer genetic tests has raised questions over what diagnosis claims are being made and how tests are regulated, report <b>Elisabeth Mahase</b> and <b>Gareth Iacobucci</b>
Prevention and Treatment of Pneumocystis Pneumonia
Authors: Alastair J.J. Wood, Henry Masur
Journal: New England Journal of Medicine (1992)

THE number of cases of Pneumocystis carinii pneumonia (PCP) recognized per year in the United States has increased dramatically, from about 65 in 1967 through 1970 to an estimated 20,000 to 60,000 in the late 1980s and early 1990s.1 , 2 This increase is largely due to the epidemic of the acquired immunodeficiency syndrome (AIDS); other contributing factors include increasing numbers of organ-transplant recipients, the use of more aggressive chemotherapy for malignant tumors and various other inflammatory or immunologic diseases, and improved diagnostic techniques.3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 The number of cases occurring annually in the United States may decline to some extent in the 1990s . . .
Tissue Destruction by Neutrophils
Authors: Franklin H. Epstein, Stephen J. Weiss
Journal: New England Journal of Medicine (1989)

WITH increasing frequency, the human neutrophil is being implicated as a mediator of tissue-destructive events in inflammatory diseases ranging from rheumatoid arthritis and myocardial reperfusion injury to respiratory distress syndromes, blistering skin disorders, and ulcerative colitis.1 , 2 In each of these diseases, as well as a variety of other acute inflammatory disorders, important components of these pathologic processes are being linked to the neutrophil's ability to release a complex assortment of agents that can destroy normal cells and dissolve connective tissues. Although these toxins normally defend the host against invading microbes, the neutrophil has little intrinsic ability to differentiate between foreign . . .
Ornithine Transcarbamylase Deficiency
Authors: Alexander G.M. Campbell, Leon E. Rosenberg, Philip J. Snodgrass, Claude T. Nuzum
Journal: New England Journal of Medicine (1973)

Three successive male infants in one family became comatose and died at less than 10 days of age. No cause for death was identified in the first boy, but striking hyperammonemia, which was due to almost complete absence of hepatic ornithine transcarbamylase activity, was found in the second and third boys. All attempts to control the hyperammonemia, including total dietary protein restriction, exchange transfusion and peritoneal dialysis, proved futile, suggesting that ornithine transcarbamylase deficiency of this magnitude is incompatible with survival. These findings are in sharp contrast to previous reports of partial ornithine transcarbamylase deficiency, noted to occur almost exclusively in females and to be compatible with long-term survival on a diet restricted in protein. Hyperammonemia resulting from almost complete ornithine transcarbamylase deficiency must now be included in the differential diagnosis of neonatal lethargy and coma.
Prenatal Genetic Diagnosis in 3000 Amniocenteses
Authors: Mitchell S. Golbus, William D. Loughman, Charles J. Epstein, Giesela Halbasch, John D. Stephens, Bryan D. Hall
Journal: New England Journal of Medicine (1979)

We analyzed 3000 consecutive amniocenteses for prenatal diagnosis to assess the frequency of abnormalities, safety of the procedure, technical and interpretive difficulties and overall diagnostic accuracy. Chromosomal abnormalities were detected in 2.4 per cent of the 2404 pregnancies tested because of advanced maternal age (≥35 years), in 1.2 per cent of 240 monitored because of prior trisomy 21 and in 9.1 per cent of 55 examined for other cytogenetic indications. Mosaicism was detected in 0.4 per cent, and unexpected translocations in 0.4 per cent. Amniotic fluid was obtained on the first attempt in 99.3 per cent of the last 1000 cases, and cultures established from 99.7 per cent of patients attending our clinic. The fluid was discolored in 1.2 per cent of patients, a quarter of whom had missed abortions. The rate of spontaneous abortion after amniocentesis was 1.5 per cent. There were 14 diagnostic errors, six serious enough to affect the outcome of pregnancy. The karyotyping error rate was 0.07 per cent. We conclude that prenatal diagnosis is safe, highly reliable and extremely accurate. (N Engl J Med 300:157–163, 1979)
Pulmonary emphysema subtypes defined by unsupervised machine learning on CT scans
Authors: Elsa D Angelini, Jie Yang, Pallavi P Balte, Eric A Hoffman, Ani W Manichaikul, Yifei Sun, Wei Shen, John H M Austin, Norrina B Allen, Eugene R Bleecker, Russell Bowler, Michael H Cho, Christopher S Cooper, David Couper, Mark T Dransfield, Christine Kim Garcia, MeiLan K Han, Nadia N Hansel, Emlyn Hughes, David R Jacobs, Silva Kasela, Joel Daniel Kaufman, John Shinn Kim, Tuuli Lappalainen, Joao Lima, Daniel Malinsky, Fernando J Martinez, Elizabeth C Oelsner, Victor E Ortega, Robert Paine, Wendy Post, Tess D Pottinger, Martin R Prince, Stephen S Rich, Edwin K Silverman, Benjamin M Smith, Andrew J Swift, Karol E Watson, Prescott G Woodruff, Andrew F Laine, R Graham Barr
Journal: Thorax (2023)

Background Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover CT emphysema subtypes with distinct characteristics, prognoses and genetic associations. Methods New CT emphysema subtypes were identified by unsupervised machine learning on only the texture and location of emphysematous regions on CT scans from 2853 participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), a COPD case–control study, followed by data reduction. Subtypes were compared with symptoms and physiology among 2949 participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study and with prognosis among 6658 MESA participants. Associations with genome-wide single-nucleotide-polymorphisms were examined. Results The algorithm discovered six reproducible (interlearner intraclass correlation coefficient, 0.91–1.00) CT emphysema subtypes. The most common subtype in SPIROMICS, the combined bronchitis-apical subtype, was associated with chronic bronchitis, accelerated lung function decline, hospitalisations, deaths, incident airflow limitation and a gene variant near DRD1 , which is implicated in mucin hypersecretion (p=1.1 ×10 −8 ). The second, the diffuse subtype was associated with lower weight, respiratory hospitalisations and deaths, and incident airflow limitation. The third was associated with age only. The fourth and fifth visually resembled combined pulmonary fibrosis emphysema and had distinct symptoms, physiology, prognosis and genetic associations. The sixth visually resembled vanishing lung syndrome. Conclusion Large-scale unsupervised machine learning on CT scans defined six reproducible, familiar CT emphysema subtypes that suggest paths to specific diagnosis and personalised therapies in COPD and pre-COPD.
Hereditary Hemolytic Anemia with Triosephosphate Isomerase Deficiency
Authors: Arthur S. Schneider, William N. Valentine, Masao Hattori, Henry L. Heins
Journal: New England Journal of Medicine (1965)

THE demonstration of the association of inherited deficiencies of erythrocyte enzymes with certain congenital hemolytic anemias has aided a greater understanding of the genetic and pathological manifestations of these disorders, and has resulted in a more definitive classification of these heterogeneous conditions. In 1954 Selwyn and Dacie1 separated the congenital nonspherocytic hemolytic anemias into two classes, Types 1 and 2, on the basis of differences in the spontaneous autohemolysis of sterile defibrinated blood. Valentine, Tanaka and Miwa,2 , 3 in 1961, described the occurrence of a marked deficiency of erythrocyte pyruvate kinase in association with hemolytic disease classifiable as Type 2 on . . .
Transplantation Immunity and the Maternal-Fetal Relation
Authors: R. E. Billingham
Journal: New England Journal of Medicine (1964)

CONFRONTATION of mammals with tissues or cells of alien genetic constitution is not restricted to the professional activities of surgeons and experimental biologists. Every pregnancy in an outbred population represents a natural parabiotic union and intimate mutual exposure of mother and fetus to each other's tissues and foreign transplantation antigens. This follows since the fetus inherits from its father a variable number of transplantation antigens that are foreign to the mother, and fails to inherit from its mother all her histocompatibility factors.The purpose of this article is to consider the relation between mother and fetus from the point of . . .
Multi-omics dissection of stage-specific artemisinin tolerance mechanisms in Kelch13-mutant Plasmodium falciparum
Authors: Jiayun Chen, Peng Gao, Wei Xiao, Guangqing Cheng, Sanjeev Krishna, Jianyou Wang, Yin Kwan Wong, Chen Wang, Liwei Gu, Dong Hua Yang, Jigang Wang
Journal: Drug Resistance Updates (2023)
DeepBreath—automated detection of respiratory pathology from lung auscultation in 572 pediatric outpatients across 5 countries
Authors: Julien Heitmann, Alban Glangetas, Jonathan Doenz, Juliane Dervaux, Deeksha M. Shama, Daniel Hinjos Garcia, Mohamed Rida Benissa, Aymeric Cantais, Alexandre Perez, Daniel Müller, Tatjana Chavdarova, Isabelle Ruchonnet-Metrailler, Johan N. Siebert, Laurence Lacroix, Martin Jaggi, Alain Gervaix, Mary-Anne Hartley, Florence Hugon, Derrick Fassbind, Makura Barro, Georges Bediang, N. E. L. Hafidi, M. Bouskraoui, Idrissa Ba
Journal: npj Digital Medicine (2023)

The interpretation of lung auscultation is highly subjective and relies on non-specific nomenclature. Computer-aided analysis has the potential to better standardize and automate evaluation. We used 35.9 hours of auscultation audio from 572 pediatric outpatients to develop DeepBreath : a deep learning model identifying the audible signatures of acute respiratory illness in children. It comprises a convolutional neural network followed by a logistic regression classifier, aggregating estimates on recordings from eight thoracic sites into a single prediction at the patient-level. Patients were either healthy controls (29%) or had one of three acute respiratory illnesses (71%) including pneumonia, wheezing disorders (bronchitis/asthma), and bronchiolitis). To ensure objective estimates on model generalisability, DeepBreath is trained on patients from two countries (Switzerland, Brazil), and results are reported on an internal 5-fold cross-validation as well as externally validated (extval) on three other countries (Senegal, Cameroon, Morocco). DeepBreath differentiated healthy and pathological breathing with an Area Under the Receiver-Operator Characteristic (AUROC) of 0.93 (standard deviation [SD] ± 0.01 on internal validation). Similarly promising results were obtained for pneumonia (AUROC 0.75 ± 0.10), wheezing disorders (AUROC 0.91 ± 0.03), and bronchiolitis (AUROC 0.94 ± 0.02). Extval AUROCs were 0.89, 0.74, 0.74 and 0.87 respectively. All either matched or were significant improvements on a clinical baseline model using age and respiratory rate. Temporal attention showed clear alignment between model prediction and independently annotated respiratory cycles, providing evidence that DeepBreath extracts physiologically meaningful representations. DeepBreath provides a framework for interpretable deep learning to identify the objective audio signatures of respiratory pathology.
Wearable based monitoring and self-supervised contrastive learning detect clinical complications during treatment of Hematologic malignancies
Authors: Malte Jacobsen, Rahil Gholamipoor, Till A. Dembek, Pauline Rottmann, Marlo Verket, Julia Brandts, Paul Jäger, Ben-Niklas Baermann, Mustafa Kondakci, Lutz Heinemann, Anna L. Gerke, Nikolaus Marx, Dirk Müller-Wieland, Kathrin Möllenhoff, Melchior Seyfarth, Markus Kollmann, Guido Kobbe
Journal: npj Digital Medicine (2023)

Serious clinical complications (SCC; CTCAE grade ≥ 3) occur frequently in patients treated for hematological malignancies. Early diagnosis and treatment of SCC are essential to improve outcomes. Here we report a deep learning model-derived SCC-Score to detect and predict SCC from time-series data recorded continuously by a medical wearable. In this single-arm, single-center, observational cohort study, vital signs and physical activity were recorded with a wearable for 31,234 h in 79 patients (54 Inpatient Cohort (IC)/25 Outpatient Cohort (OC)). Hours with normal physical functioning without evidence of SCC (regular hours) were presented to a deep neural network that was trained by a self-supervised contrastive learning objective to extract features from the time series that are typical in regular periods. The model was used to calculate a SCC-Score that measures the dissimilarity to regular features. Detection and prediction performance of the SCC-Score was compared to clinical documentation of SCC (AUROC ± SD). In total 124 clinically documented SCC occurred in the IC, 16 in the OC. Detection of SCC was achieved in the IC with a sensitivity of 79.7% and specificity of 87.9%, with AUROC of 0.91 ± 0.01 (OC sensitivity 77.4%, specificity 81.8%, AUROC 0.87 ± 0.02). Prediction of infectious SCC was possible up to 2 days before clinical diagnosis (AUROC 0.90 at -24 h and 0.88 at -48 h). We provide proof of principle for the detection and prediction of SCC in patients treated for hematological malignancies using wearable data and a deep learning model. As a consequence, remote patient monitoring may enable pre-emptive complication management.